Field of the Invention
The present invention relates to methods of determining if a subject has an increased risk of suffering from memory impairment. The methods comprise analyzing at least one plasma sample from the subject to determine a value of the subject's lipidomic profile, and comparing the value of the subject's lipidomic profile with the value of a normal lipidomic profile. A decrease in the value of the subject's lipidomic profile over normal values is indicative that the subject has an increased risk of suffering from memory impairment compared to a normal individual.
Background of the Invention
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive dementia that insidiously and inexorably robs older adults of their memory and other cognitive abilities. The prevalence of AD is expected to double every 20 years from 35.6 million individuals worldwide in 2010 to 115 million affected individuals by 2050. There is no cure and current therapies are unable to slow the disease progression.
Early detection of the at-risk population (preclinical), or those in the initial symptomatic stages (prodromal) of AD, may present opportunities for more successful therapeutic intervention, or even disease prevention by interdicting the neuropathological cascade that is characterized by the deposition of extracellular β-amyloid (Aβ) and accumulation of intracellular fibrils of microtubular hyperphosphorylated tau protein within the brain. Biomarkers for early disease, including cerebrospinal fluid (CSF) tau and Aβ levels, structural and functional magnetic resonance imaging (MRI), and the recent use of brain amyloid imaging, are of limited use for widespread screening since they provide diagnostic options that are either invasive, i.e., require lumbar puncture, time-consuming, i.e., several hours in a scanner for most comprehensive imaging protocols, or expensive. No current blood-based biomarkers can detect incipient dementia with the required sensitivity and specificity at a preclinical stage. Continued interest in blood-based biomarkers remains because these specimens are obtained using rapid, minimally invasive methods. With recent technological advances in ‘omics’ and systems level approaches, the comprehensive bioinformatic analyses of prognostic biomarkers may yield new insights into the underlying mechanisms and pathobiological networks of AD and possibly herald the development of new therapeutic strategies.
The preclinical interval resulting in mild cognitive impairment (MCI) or AD is known to be variable, multifactorial, and extends up to 7-10 years prior to the emergence of clinical signs. In the absence of valid and reliable biomarkers, multimodal neurocognitive testing remains the most accurate, standardized, and widely used pre-mortem screening method to determine clinical MCI or AD. The utility of strict cognitive assessment for preclinical states of MCI or AD is limited, however, as this approach is time-consuming and expected to be present almost all individuals as normal, as it quantitatively delineates specific brain properties, such as language, thought, and behavior, which is typically not affected in individual in the preclinical state. Thus, information obtained from multiple diagnostic studies will probably be most useful in defining the MCI/AD preclinical state, including neuropsychological testing and some form(s) of biomarker(s). While CSF and neuroimaging have been used to define preclinical MCI/AD to date, their clinical utility as screening tools for asymptomatic individuals is not established.